A Phase 1 Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics, With an Open-Label Target Occupancy Study of BIIB113 in Healthy Participants

Parts A and B: The primary objective of this study is to evaluate the safety and tolerability of single and multiple ascending oral doses of BIIB113 in healthy participants. The secondary objectives of this study are to evaluate the single and multiple oral dose pharmacokinetic (PK) profile of BIIB113 in healthy participants and to evaluate the effect of food on the single oral dose of BIIB113 in healthy participants of Part A cohort 3.
Part C: The primary objectives of this study are to evaluate the safety and tolerability of single and multiple ascending oral doses of BIIB113 in healthy participants and to determine target occupancy (TO) as measured by O-GlcNAcase-Positron Emission Tomography (OGA-PET) of single and multiple oral doses of BIIB113 in healthy participants.

开始日期2022-01-24

申办/合作机构

Biogen, Inc.

100 项与 BIIB-113 相关的临床结果

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100 项与 BIIB-113 相关的转化医学

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100 项与 BIIB-113 相关的专利（医药）

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项与 BIIB-113 相关的文献（医药）

2026-01-01·JPAD-Journal of Prevention of Alzheimers Disease

Erratum to “Results of the first-in-human, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study of BIIB113 in healthy volunteers” [The Journal of Prevention of Alzheimer's Disease volume 12 (2025) 100302]

作者: Nery, Flavia C ; Wilkes, Denisa ; Arnold, H Moore ; Landen, Jaren ; Yachnin, Jeffrey ; Suttle, Ben ; Wu, Shuang ; Bullain, Szofia ; Varrone, Andrea ; Jones, Lori ; Hirschhorn, Beth ; Nag, Sangram ; Curiale, Gioacchino ; Gallagher, Diana ; Stenkrona, Per ; Xie, Jing ; Bolin, Martin ; Singh, Dave ; Halldin, Christer ; Yesilalan, Esin ; Kaliszczak, Maciej ; Morén, Anton Forsberg ; Hering, Heike

2025-09-01·JPAD-Journal of Prevention of Alzheimers Disease

Results of the first-in-human, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study of BIIB113 in healthy volunteers

Article

作者: Nery, Flavia C ; Wilkes, Denisa ; Landen, Jaren ; Arnold, H Moore ; Yachnin, Jeffrey ; Wu, Shuang ; Suttle, Ben ; Bullain, Szofia ; Varrone, Andrea ; Hirschhorn, Beth ; Jones, Lori ; Curiale, Gioacchino ; Nag, Sangram ; Gallagher, Diana ; Stenkrona, Per ; Xie, Jing ; Singh, Dave ; Bolin, Martin ; Halldin, Christer ; Yesilalan, Esin ; Kaliszczak, Maciej ; Morén, Anton Forsberg ; Hering, Heike

BACKGROUND:

Preclinical studies have demonstrated that inhibition of the O-linked β-N-acetylglucosaminidase enzyme increases tau O-linked β-N-acetylglucosaminylation and may attenuate tau pathology in Alzheimer's disease.

OBJECTIVES:

To examine the safety, tolerability, pharmacokinetics, and target occupancy of single- and multiple-ascending oral doses of the small-molecule O-linked β-N-acetylglucosaminidase inhibitor, BIIB113.

DESIGN:

Study 276HV101 was a first-in-human, multicenter, Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose trial.

SETTING:

72 participants were enrolled from February 2022 through July 2023.

PARTICIPANTS:

Adult healthy female and infertile/vasectomized male participants.

INTERVENTION:

In the single-ascending dose substudy, participants received a single dose of placebo or BIIB113 0.5, 3, 15, or 50 mg. In the 14-day multiple-ascending dose substudy, participants received placebo or BIIB113 15 or 50 mg once daily. In the target occupancy substudy, participants received either a single dose of BIIB113 0.5 or 3 mg or a once-daily dose of BIIB113 0.5 mg.

MEASUREMENTS:

Safety and tolerability were measured by incidence of adverse events. Pharmacokinetic and concentration-time profiles were assessed. Target occupancy was evaluated using the carbon-11 BIO-1819,578 radioligand.

RESULTS:

BIIB113 was generally well tolerated. Pharmacokinetics were linear over the dose range, with a half-life of approximately 30 h. Administration with food decreased the rate but did not affect the extent of absorption. There were no clinically meaningful differences in pharmacokinetics between elderly and nonelderly participants. Multiple once-daily doses of BIIB113 0.5 mg maintained a target occupancy of ≥90 % up to 48 h.

CONCLUSIONS:

BIIB113 was well tolerated and achieved high levels of target occupancy.

项与 BIIB-113 相关的新闻（医药）

2025-11-26

·腾讯网

勇闯“死亡谷”的中国药企越来越多，能否破局？

每经记者：林姿辰每经编辑：魏官红被称为医药研发“死亡谷”的阿尔茨海默病（AD），有何魔力？11月24日晚间，丹麦制药巨头诺和诺德宣布，针对司美格鲁肽（Semaglutide）治疗阿尔茨海默病的两项大型Ⅲ期试验均未达到主要目标；而在不久前，中国药企绿叶制药宣布，公司自研的LY03017已获得美国食品药品监督管理局（FDA）许可开展临床试验，其中的一项适应证与阿尔茨海默病有关。这并不是个例。近日，康方生物自研的AK152获批临床，用于治疗阿尔茨海默病，成为国内首个进入临床阶段的AD双抗药物；恒瑞医药的SHR-1707，作为国内首个自研抗Aβ单抗，已经进入Ⅱ期临床阶段；先通医药、原子高科等致力于AD早期诊断的药企研发也在路上。一方面，跨国药企在AD药物研发和商业化的道路上屡次受挫；另一方面，中国药企对这一领域的研发热情日益高涨。后者有希望成为全球AD治疗领域的新破局者吗？中国在研药物全球第二11月24日，诺和诺德公布了口服GLP-1药物司美格鲁肽针对早期阿尔茨海默病患者进行的Evoke（试验代号名）和Evoke+（试验代号名）Ⅲ期试验的顶线结果，两项试验均未证实司美格鲁肽在减缓阿尔茨海默病进展方面优于安慰剂。此前，辉瑞、罗氏、强生、渤健等跨国药企，均有在阿尔茨海默病领域折戟的经历，其根本原因在于阿尔茨海默病的病因和发病机制仍未明确，即便主流的Aβ与tau蛋白异常假说也屡遭质疑。在跨国药企中，渤健和礼来一直是神经疾病药物研发领域的领头羊，但双方都在2025年砍掉了阿尔茨海默病的研发管线，前者砍掉的BIIB113项目是一款旨在通过阻止tau蛋白聚集，治疗早期阿尔茨海默病的口服小分子药物，礼来砍掉的LY3372689，同样是一款口服抗tau药物，去年8月，公司宣布该药物在治疗早期症状性AD的Ⅱ期研究中失败。与此形成对比的是，中国药企在AD药物研发领域热情高涨。去年，智慧芽全球新药数据库显示，中国针对AD适应证药物研发的数量仅次于美国，排在全球第二位。据《每日经济新闻》记者统计，截至目前，中国原创AD在研药物包括恒瑞医药的SHR-1707（抗Aβ单克隆抗体）、康方生物的AK152（靶向Aβ和BBB高表达受体的双特异性抗体）、绿叶制药的LY03017（5-HT2AR反向激动剂/5-HT2CR拮抗剂）、深圳理工大学的BrAD-R13片（口服TrkB受体激动剂）、卓凯生物的50561片（Rac1抑制剂）等。中国药企为何勇于布局？尽管中国药企对AD药物的研发热情有所升温，但跨国药企得益于多年积累，仍“掌握”着全球AD药物市场。根据2022年5月发表于《中国合理用药探索》的文章《阿尔茨海默病的发病机制和药物研发进展》，全球获批上市的AD原创药物几乎都来自外国药企，仅甘露特纳一款由中国药企研发、获国家药品监督管理局（NMPA）“全球首批”。但今年6月，甘露特纳传出停产消息。在全球范围，记者注意到，由于两个Ⅲ期临床试验结果互相矛盾，临床获益并不明确，阿杜那单抗于2024年1月31日退出了AD治疗的舞台。另外，卫材/渤健联合研发的仑卡奈单抗（Lecanemab）、礼来的多奈单抗（Donanemab）分别于2023年和2024年在美获批，这是全球“唯二”获批的治疗Aβ抗体药物。实际上，跨国药企的几款AD新药战绩并不是很好。去年3月，卫材公司预期仑卡奈单抗在2027财年的销售额约为5000亿日元（约33.3亿美元），但最新预期为2500亿日元到2800亿日元（约合16.65亿美元至18.65亿美元）；而礼来的多奈单抗遭到英国医保监管机构拒绝，原因是监管机构认为该药物的益处太小，不足以证明其价格合理。在此背景下，国内药企的研发信心源于何处？11月24日，绿叶制药方面接受了《每日经济新闻》记者采访，在公司看来，有临床需求和技术进步两方面原因在推动。一方面，当前AD诊疗技术已显著成熟，生物标志物检测（如脑脊液Aβ、tau蛋白）、多模态医学影像（如PET-CT、MRI）与标准化临床症状量表（如MMSE、NPI）的结合，大幅提升了AD的诊断精准度，已从技术层面缓解了行业性诊断难题。另一方面，AD领域内有庞大且未被满足的刚性需求。以公司布局的ADP（阿尔茨海默病精神病性障碍）为例，25%至50%的阿尔茨海默病患者会在疾病病程中出现该精神症状，但目前该领域没有获批药物。公司日前发布的公告显示，FDA豁免了LY03017在Ⅰ期临床试验中单次给药剂量递增（SAD）试验环节，该药物后续可直接启动多次给药剂量递增（MAD）以及后续的临床试验。不过，记者注意到，绿叶制药在国内、美国开展的临床试验，后续可能不仅仅针对ADP这一个适应证，而是同步推进ADP、帕金森病精神病性障碍（PDP）、精神分裂症阴性症状（NSS）三个适应证的研究。在排序上，公司方面表示，将基于临床进展动态优化推进节奏。每日经济新闻

临床2期临床3期临床失败申请上市

2025-03-05

·Pharmaceutical Technology

Asceneuron halts Alzheimer’s trial adding to tau-targeting setbacks

A build-up of the abnormal tau can contribute to Alzheimer’s disease symptoms. Credit: Andrew Brookes via Getty Images. After Eli Lilly and Biogen’s setbacks in developing O-GlaNAcase (OGA) inhibitors for Alzheimer’s disease, Asceneuron has now halted its own Phase II trial of ASN51, its experimental oral OGA inhibitor. The company disclosed the decision in an update to the federal clinical trials database ClinicalTrials.gov , describing it as “strategic” without providing further details. The trial, which kicked off in October 2024, was expected to run for two years. The study (NCT06677203) was set to evaluate two doses of ASN51 against a placebo in 123 patients with early Alzheimer’s, focusing on safety, tolerability, suicide severity assessment through the Columbia-Suicide Severity Rating Scale (C-SSRS), and tau protein levels in cerebrospinal fluid. Asceneuron had previously said that ASN51 could be a disease-modifying therapy, with applications beyond Alzheimer’s in diseases such as Parkinson’s and amyotrophic lateral sclerosis (ALS). The decision to move ASN51 into this Phase II study was supported by a $100m Series C funding round announced in July 2024. The financing was led by Novo Holdings, the controlling shareholder of Novo Nordisk. Novo Holdings’ senior partner for venture investments Naveed Siddiqi described ASN51 as offering “the potential paradigm shift” in Alzheimer’s treatment at the time of the funding round. Asceneuron had already demonstrated in multiple Phase I studies that ASN51 reaches the nervous system and impacts the OGA enzyme. OGA inhibitors have been explored as a potential new class of disease-modifying treatments for Alzheimer’s and other neurodegenerative diseases due to their ability to target tau protein accumulation. Unlike amyloid-targeting therapies – such as Eisai and Biogen’s Leqembi (lecanemab) – that have dominated Alzheimer’s drug development, OGA inhibitors aim to slow disease progression by preventing the buildup of toxic tau aggregates in the brain. This termination follows setbacks for other OGA inhibitors in development. In August 2024, Eli Lilly disclosed that its OGA inhibitor, LY3372689, failed to meet the primary endpoint in a Phase II trial (NCT05063539) for early symptomatic Alzheimer’s. The study did not show a statistically significant benefit in slowing disease progression as measured by the integrated Alzheimer’s Disease Rating Scale (iADRS). Lilly also previously abandoned its antibody-based tau inhibitor zagotenemab in 2021 while Roche discontinued the development of semorinemab in January 2024. Last month, Biogen discontinued an early-stage OGA inhibitor programme, BIIB113. Beyond ASN51, Asceneuron has another OGA inhibitor, ASN90, which it licensed to Ferrer in February 2023. ASN90 is currently in a Phase II trial (NCT06355531) for progressive supranuclear palsy, a rare tau-related neurodegenerative disorder.

临床2期临床1期临床结果

2025-03-01

·思齐俱乐部

辉瑞、渤健接连削减研发管线！

新药研发风险高，投入大，回报周期长，早已让药企砍管线成为常态。而近年来，出于资源配置和资金聚集的问题，医药企业的降本大刀更是频频挥向新药研发管线。近期，辉瑞、渤健、礼来等跨国药企就已相继终止了多款高价新药的开发。近日，有报道称，辉瑞宣布将终止B型血友病基因疗法Beqvez的开发和商业化。这款定价高达350万美元的基因疗法，从获批到被放弃，仅仅过了一年的时间。公开资料显示，该疗法的研发始于Spark Therapeutics，辉瑞在2014年从Spark获得了Beqvez的授权。2024年1月，Beqvez获得加拿大卫生部批准上市，用于治疗18岁或以上中重度至重度血友病B成人患者；2024年4月，Beqvez获得美国FDA批准上市。据悉，放弃Beqvez后，辉瑞打算将其资源集中在其认为将对患者产生重大影响的治疗方法上，例如近期获得批准的一种血友病A新药Hympavzi上。Hympavzi是一种抗组织因子途径抑制剂(TFPI)。 2月12日，渤健(Biogen)宣布终止4款神经类药物的开发，包括针对糖尿病周围神经性疼痛的BIIB143(cemdomespib)、针对早期阿尔茨海默病的BIIB113、针对早期帕金森的BIIB094和针对多系统萎缩症的BIIB101。在此之前，礼来也透露，在2024年第四季度，其已对两个主要治疗领域的研发管线进行优化，终止了处于临床阶段的阿尔茨海默病和肥胖症候选药物项目。其中，礼来的口服O - GlcNAcase抗tau蛋白药物cepemgnastat在一项2期试验中未能减缓早期症状性阿尔茨海默病患者的临床衰退，数月后，就已从研发管线中被移除。除了跨国药企，近年来还有上海医药、华东医药、科兴制药、亚虹医药、天坛生物、天士力等众多国内药企也先后终止了在研项目。其中，多数管线被叫停的原因包括临床试验结果未达预期、缺乏市场竞争力，以及外部环境变化导致的药品需求下降等。业内表示，这些药企终止药物开发的案例，反映出药企在新药开发和商业化上一直都在面临重大挑战。未来，在政策的引导和市场竞争加剧的情况下，药企对于管线的管理需更加理性、谨慎。来源：制药网点击阅读原文了解更多

上市批准基因疗法临床2期

100 项与 BIIB-113 相关的药物交易

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